Therapeutisches Drug Monitoring von Antiinfektiva bei Intensivpatienten – für welche Arzneistoffe und wie?

Was ist neu?

Prinzip des therapeutischen Drug Monitorings Für immer mehr Antiinfektiva gibt es Erkenntnisse zur Expositions-Wirkungs-Beziehung, die im therapeutischen Drug Monitoring (TDM) genutzt werden können. Dabei spielt die Schätzung der AUC (area under the curve) eine wichtige Rolle. Eine spezielle Pharmakokinetik-Software hilft in der Praxis, die Schätzung der AUC auch anhand weniger Proben zu ermöglichen.

Für welche Arzneistoffe wird ein therapeutisches Drug Monitoring empfohlen? Neben dem vielfach bereits etablierten TDM für Aminoglykoside (Amikacin, Gentamicin und Tobramycin) und Glykopeptide (Vancomycin, Teicoplanin) empfiehlt ein fachübergreifendes Expertengremium bei Intensivpatienten ein TDM für Betalaktame, Linezolid und Voriconazol. Neuerungen gibt es auch bei Vancomycin, bei dem vom häufig praktizierten „Talspiegel“-TDM zum in klinischen Studien überlegenen AUC-basierten TDM übergegangen werden soll.

Abstract

Pharmacokinetic and pharmacodynamic changes in intensive care unit patients can increase the risk for therapeutic failure or adverse effects of anti-infective therapy. Therapeutic drug monitoring (TDM) can inform required dose adaptions. The present article reviews the current practice and outlines modern approaches for decision making such as model-informed precision dosing software using the area-under-the-concentration-time-curve as target in favor of simplistic decision making based on trough concentrations. Moreover, the current recommendations for performing TDM of beta-lactams, aminoglycosides, linezolid, glycopeptides and voriconazole are concisely summarized.

Schlüsselwörter

Dosierung - therapeutisches Drug Monitoring - Antibiotika - Pharmakokinetik - Pharmakodynamik

Key words

dosing - therapeutic drug monitoring - antibiotics - pharmacokinetics - pharmacodynamics

Publikationsverlauf

Artikel online veröffentlicht:
30. November 2020

• Literatur

• 1 Abdul-Aziz MH, Alffenaar JWC, Bassetti M. et al. Antimicrobial therapeutic drug monitoring in critically ill adult patients: a Position Paper. Intensive Care Med 2020; 46: 1127-1153
• 2 Roberts JA, Abdul-Aziz MH, Lipman J. et al. Individualised antibiotic dosing for patients who are critically ill: challenges and potential solutions. Lancet Infect Dis 2014; 14: 498-509
• 3 Gonçalves-Pereira J, Póvoa P. Antibiotics in critically ill patients: a systematic review of the pharmacokinetics of β-lactams. Crit Care 2011; 15: R206
• 4 Wong G, Briscoe S, McWhinney B. et al. Therapeutic drug monitoring of β-lactam antibiotics in the critically ill: direct measurement of unbound drug concentrations to achieve appropriate drug exposures. J Antimicrob Chemother 2018; 73: 3087-3094
• 5 Mahmoud S, Shen C. Augmented Renal Clearance in Critical Illness: An Important Consideration in Drug Dosing. Pharmaceutics 2017; 9: 36
• 6 Roehr AC, Frey OR, Koeberer A. et al. Anti-Infective Drugs during Continuous Hemodialysis -Using the Bench to Learn What to do at the Bedside. Int J Artif Organs 2015; 38: 17-22
• 7 Keller F. Pharmacotherapy and kidney dysfunction. Med Klin Intensivmed Notfmed 2019; 114: 444-451
• 8 Craig W. Basic pharmacodynamics of antibacterials with clinical applications to the use of β-lactams, glycopeptides, and linezolid. Infect Dis Clin North Am 2003; 17: 479-501
• 9 Weiner LM, Webb AK, Limbago B. et al. Antimicrobial-Resistant Pathogens Associated With Healthcare-Associated Infections: Summary of Data Reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2011–2014. Infect Control Hosp Epidemiol 2016; 37: 1288-1301
• 10 Wicha SG, Kees MG, Solms A. et al. TDMx: A novel web-based open-access support tool for optimising antimicrobial dosing regimens in clinical routine. Int J Antimicrob Agents 2015; 45: 442-444
• 11 Gao Y, Hennig S, Barras M. Monitoring of Tobramycin Exposure: What is the Best Estimation Method and Sampling Time for Clinical Practice?. Clin Pharmacokinet 2019; 58: 389-399
• 12 Shingde RV, Reuter SE, Graham GG. et al Assessing the accuracy of two Bayesian forecasting programs in estimating vancomycin drug exposure. J Antimicrob Chemother 2020; 75: 3293-3302 . doi:10.1093/jac/dkaa320
• 13 De Winter S, Wauters J, Meersseman W. et al. Higher versus standard amikacin single dose in emergency department patients with severe sepsis and septic shock: a randomised controlled trial. Int J Antimicrob Agents 2018; 51: 562-570
• 14 Neely MN, Kato L, Youn G. et al. A prospective trial on the use of trough concentration versus area under the curve (AUC) to determine therapeutic vancomycin dosing. Antimicrob Agents Chemother 2017; 62: e02042-17
• 15 Rybak MJ, Le J, Lodise TP. et al. Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: A revised consensus guideline and review by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatr. Am J Heal Pharm 2020; 77: 835-863
• 16 Zhou L, Gao Y, Cao W. Retrospective analysis of relationships among the dose regimen, trough concentration, efficacy, and safety of teicoplanin in chinese patients with moderate-severe gram-positive infections. Infect Drug Resist 2018; 11: 29-36
• 17 Rayner CR, Forrest A, Meagher AK. et al. Clinical Pharmacodynamics of Linezolid in Seriously Ill Patients Treated in a Compassionate Use Programme. Clin Pharmacokinet 2003; 42: 1411-1423
• 18 Ueda K, Nannya Y, Kumano K. et al. Monitoring trough concentration of voriconazole is important to ensure successful antifungal therapy and to avoid hepatic damage in patients with hematological disorders. Int J Hematol 2009; 89: 592-599
• 19 Troke PF, Hockey HP, Hope WW. Observational Study of the Clinical Efficacy of Voriconazole and Its Relationship to Plasma Concentrations in Patients. Antimicrob Agents Chemother 2011; 55: 4782-4788